Increased expression of Tbet in CD4+ T cells from clinically isolated syndrome patients at high risk of conversion to clinically definite MS.

Abstract

Background: The ability to identify clinically isolated syndrome (CIS) patients at high risk of progression to clinically definite multiple sclerosis (CDMS) would be clinically beneficial. The initiation of T cell mediated autoimmune diseases such as multiple sclerosis (MS) requires the initial inappropriate activation and differentiation of auto-reactive CD4 + T cells. The quiescence of naive T cells is actively maintained by molecules such as TOB1, which control the threshold of activation. Upon activation, CD4 + T cells can differentiate into various subsets depending on the milieu present. Th1 and Th17 cells are strongly implicated in MS, while regulatory T (Treg) cells constrain autoimmune inflammation and prevent autoimmunity. Findings: We therefore investigated the expression of TOB1, CD44 and Treg, Th1 and Th17 transcription factors in relation to CIS progression. The expression of TOB1 , CD44 , FOXP3 , TBX21 and RORC genes were measured in CD4 + T cells from 10 healthy controls, 20 CIS patients within 3 months of initial clinical presentation and 10 relapsing remit - ting MS patients sampled within 2 months of relapse. CIS patients were subsequently grouped into those who con- verted to CDMS within 1 year and those who remained CIS. No differences in the expression of TOB1 , CD44 , FOXP3 and RORC were observed. There was a significant increase in the expression of the Th1 transcription factor Tbet, encoded by TBX21 , in CIS patients that converted within 1 year compared with those who did not. Conclusion: This pilot data suggests a role for Th1 cells in CIS progression and warrants further evaluation in a larger cohort.